We model all different aspects of μ-opioid receptor activation. This starts with the binding of an opioid to the receptor, followed by conformnational changes, spatio-temporal resolved signaling processes in the cell, the signaling effects, and the internalization and recovering of the μ-opioid receptor via the arrestin route. For this goal we need to model non-reversible molecular and signaling processes. The scientific goal is to estimate missing parameters, characteristic time-scales of the elementary steps, and coherent structures of  non-reversible processes from (also experimental) data.

Figure 1: Reaction network for the signaling pathway. The receptor cycle is connected to the G-protein cycle and further to the signal cycle of membrane calcium channel modulation. We analyze the effect of NFEPP in comparison to fentanyl at different pH-levels and oxygen radical levels. The dynamics are studied using deterministic models in form of reaction rate equations and by stochastic models in form of Markov jump processes. 

Figure 2: Experimental in vitro data and optimally fitted ODE model. Dots represent the time course of ligand-induced G-protein subunit dissociation measured by FRET in HEK293 cells. FRET values were transformed into concentration of undissociated G-proteins by a scaling factor. Lines indicate the best-fit of the ODE model to the data.

 

 

Publications

2024
Partial mean-field model for neurotransmission dynamics Mathematical Biosciences, Vol.369, 2024 Alberto Montefusco, Luzie Helfmann, Toluwani Okunola, Stefanie Winkelmann, Christof Schütte BibTeX
arXiv
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
2023
Coarse Grained MD Simulations of Opioid interactions with the µ-opioid receptor and the surrounding lipid membrane Biophysica, 3(2), pp. 263-275, 2023 Sourav Ray, Konstantin Fackeldey, Christoph Stein, Marcus Weber BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Handlungsempfehlung zur integrativen Bewertung der weitergehenden Abwasserbehandlung von kommunalen Kläranlagen Christian Wilhelm (Ed.), DWA / GDCh, 2023, ISBN: 978-3-96862-563-8 Thomas Ternes, Karl-Heinz Bauer, Frank Brauer, Jörg Drewes, Adriano Joss, Georg Hiller, Kevin Jewell, Jörg Oehlmann, Michael Radke, Ulrike Schulte-Oehlmann, Thomas Schwartz, Peter Seel, Jeanette Völker, Lilo Weber, Marcus Weber BibTeX
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design Scientific Reports, 13(607), 2023 Arne Thies, Vikram Sunkara, Sourav Ray, Hanna Wulkow, M. Özgür Celik, Fatih Yergöz, Christof Schütte, Christoph Stein, Marcus Weber, Stefanie Winkelmann BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
2022
Cyanine Dye Coupling Mediates Self-assembly of a pH Sensitive Peptide into Novel 3D Architectures Angewandte Chemie, 61(48), p. e202208647, 2022 Rita Fernandes, Suvrat Chaowdhary, Noureldin Saleh, Natalia Mikula, Katerina Kanevche, Hans Berlepsch, Naoki Hosogi, Joachim Heberle, Marcus Weber, Christoph Böttcher, Beate Koksch BibTeX
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
SepFree NMF: A Toolbox for Analyzing the Kinetics of Sequential Spectroscopic Data Algorithms, 15(9), p. 297, 2022 Renata Sechi, Konstantin Fackeldey, Surahit Chewle, Marcus Weber BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
The Impact of Membrane Protein Diffusion on GPCR Signaling Cells, 11(10), p. 1660, 2022 Horst-Holger Boltz, Alexei Sirbu, Nina Stelzer, Primal de Lanerolle, Stefanie Winkelmann, Paolo Annibale BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
2021
A probabilistic algorithm for aggregating vastly undersampled large Markov chains Physica D: Nonlinear Phenomena, Vol.416, 2021 (preprint available as ZIB-Report 20-21) Andreas Bittracher, Christof Schütte PDF (ZIB-Report)
BibTeX
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The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Computing the minimal rebinding effect for non-reversible processes Multiscale Modeling and Simulation, 19(1), pp. 460-477, 2021 Susanne Röhl, Marcus Weber, Konstantin Fackeldey BibTeX
arXiv
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Dimensionality Reduction of Complex Metastable Systems via Kernel Embeddings of Transition Manifolds Journal of Nonlinear Science, Vol.31, 2021 Andreas Bittracher, Stefan Klus, Boumediene Hamzi, Christof Schütte BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Exploring the locking stage of NFGAILS amyloid fibrillation via transition manifold analysis The European Physical Journal B, Vol.94, 2021 Andreas Bittracher, Johann Moschner, Beate Koksch, Roland Netz, Christof Schütte BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design ZIB-Report 21-19 Sourav Ray, Arne Thies, Vikram Sunkara, Hanna Wulkow, Özgür Celik, Fatih Yergöz, Christof Schütte, Christoph Stein, Marcus Weber, Stefanie Winkelmann PDF
BibTeX
URN
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection Viruses, 13(12), p. 2456, 2021 Wolfgang Bauer, Marcus Weber, Eva Diehl-Wiesenecker, Noa Galtung, Monika Prpic, Rajan Somasundaram, Rudolf Tauber, Jochen Schwenk, Patrick Micke, Kai Kappert BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Quantitative spectroscopy of single molecule interaction times Optic Letters, 46(7), pp. 1538-1541, 2021 Horst-Holger Boltz, Alexei Sirbu, Nina Stelzer, Martin J. Lohse, Christof Schütte, Paolo Annibale BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
2020
A weak characterization of slow variables in stochastic dynamical systems Advances in Dynamics, Optimization and Computation. Series: Studies in Systems, Decision and Control. A volume dedicated to Michael Dellnitz on the occasion of his 60th birthday, Vol.304, pp. 132-150, Oliver Junge, O. Schütze, Gary Froyland, S. Ober-Blobaum, E. Padberg-Gehle (Eds.), Springer International, 2020, ISBN: 978-3-030-51264-4 Andreas Bittracher, Christof Schütte BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Data-driven approximation of the Koopman generator: Model reduction, system identification, and control Physica D: Nonlinear Phenomena, Vol.406, 2020 (epub ahead of print) Stefan Klus, Feliks Nüske, Sebastian Peitz, Jan-Hendrik Niemann, Cecilia Clementi, Christof Schütte BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Generalisierte Markov-Modellierung Springer Spektrum, Wiesbaden, 2020, ISBN: 978-3-658-29711-4 Bernhard Reuter BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
How to calculate pH-dependent binding rates for receptor-ligand systems based on thermodynamic simulations with different binding motifs ZIB-Report 20-18 (Molecular Simulation, 46:18, 1443-1452) Sourav Ray, Vikram Sunkara, Christof Schütte, Marcus Weber PDF
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The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
ISOKANN: Invariant subspaces of Koopman operators learned by a neural network The Journal of Chemical Physics, 153(11), p. 114109, 2020 Robert Julian Rabben, Sourav Ray, Marcus Weber BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Single molecule mu-opioid receptor membrane-dynamics reveal agonist-specific dimer formation with super-resolved precision Nature Chemical Biology, Vol.16, pp. 946-954, 2020 Jan Möller, Ali Isbilir, Titiwat Sungkaworn, Brenda Osberg, Christos Karathanasis, Vikram Sunkara, Eugene O Grushevsky, Andreas Bock, Paolo Annibale, Mike Heilemann, Christof Schütte, Martin J. Lohse BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Singular Value Decomposition of Operators on Reproducing Kernel Hilbert Spaces Advances om Dynamics, Optimization and Computation. Series: Studies in Systems, Decision and Control. A volume dedicated to Michael Dellnitz on his 60th birthday, Vol.304, pp. 109-131, Oliver Junge, O. Schütze, Gary Froyland, S. Ober-Blobaum, K. Padberg-Gehle (Eds.), Springer International, 2020, ISBN: 978-3-030-51264-4 Mattes Mollenhauer, Ingmar Schuster, Stefan Klus, Christof Schütte BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
2019
Fréchet differentiable drift dependence of Perron–Frobenius and Koopman operators for non-deterministic dynamics Nonlinearity, 32(11), pp. 4232-4257, 2019 Péter Koltai, Han Cheng Lie, Martin Plonka BibTeX
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The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Hybrid Models and Simulations of Reaction-Diffusion Processes Master's thesis, Freie Universität Berlin, Frank Noe (Advisor), 2019 Margarita Kostré BibTeX
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor
Kernel methods for detecting coherent structures in dynamical data Chaos: An Interdisciplinary Journal of Nonlinear Science, 29(12), 2019 Stefan Klus, Brooke E. Husic, Mattes Mollenhauer, Frank Noe BibTeX
DOI
The spatio-temporal modelling of mechanisms underlying pain relief via the µ-opioid receptor